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Shikonin, a naphthoquinone compound extracted from the root of Lithospermum erythrorhizon, has been extensively studied for its antitumor activity. Selleckchem GSK690693 However, the systematic pathways involved in Shikonin intervention in human colon cancer has not yet clearly defined.
This study was to evaluate the cytotoxic effects of Shikonin in colon cancer, as well as investigate the potential biomarkers from a global perspective and the possible antitumor mechanisms involved.
In this work, cell viability, cell cycle and cell apoptosis in human colon cancer cells were assessed to evaluate the antitumor activity of Shikonin. Transcriptomics and metabolomics were integrated to provide the perturbed pathways and explore the potential mechanisms. The crucial proteins and genes involved were further validated by immunohistochemistry and real-time quantitative PCR.
Shikonin revealed a remarkable antitumor potency in colon cancer. Cell cycle was significantly arrested at the S phase as well as apoptosis was induced in SW480 cell line. Furthermore, a total of 1642 differentially expressed genes and 40 metabolites were detected after Shikonin intervention. The integrated analysis suggested that the antitumor effect was mainly attributed to purine metabolism, arginine biosynthesis, pyrimidine metabolism, urea cycle and metabolism of amino acids. The up-regulated expression of proteins vital for arginine biosynthesis was subsequently validated by immunohistochemistry in xenograft mice. Notably, supplemental dNTPs and arginine could significantly reverse the cytotoxic effect induced by Shikonin and the genes participating in purine metabolism and arginine biosynthesis were further determined by RT-qPCR.
Our findings provide a systematic perspective in the therapeutic effect of Shikonin which might lay a foundation for further research on Shikonin in colon cancer.
Our findings provide a systematic perspective in the therapeutic effect of Shikonin which might lay a foundation for further research on Shikonin in colon cancer.
To evaluate the correlation between cycle threshold (Ct) value and occurrence of olfactory and taste dysfunction in COVID-19 patients.
This comparative study included COVID-19 patients diagnosed by reverse transcription- polymerase chain reaction (RT-PCR) based test at our hospital with mild to moderate disease. The demographic details and detailed clinical history of the patient, including history of loss of smell and taste was taken at the time of presentation. The patients were divided into 2 groups, group A COVID-19 patients with OTD; group B COVID-19 patients without OTD. 100 contiguous patients were recruited in each group. The COVID-19 test by RT-PCR was done and Ct value of the 3 genes E (Envelope encoding) gene, N (Nucleocapsid encoding) gene, and RdRp (RNA-dependent RNA polymerase) gene, was used for data analysis. The Ct values of each of the three genes were compared between groups A and B.
Group A and B did not differ significantly in terms of basic demographics. The differences in the Ct values of the 3 genes E gene, N gene and RdRp gene, of group A and B were found to be statistically significant (p=0.005, p=0.001 and p=0.002, respectively).
The patients with OTD had a lower Ct value at diagnosis, and hence, a higher viral load than those without OTD. The evaluation of Ct value and viral load in COVID-19 patients may help in further reducing the transmission of the virus in the community.
The patients with OTD had a lower Ct value at diagnosis, and hence, a higher viral load than those without OTD. The evaluation of Ct value and viral load in COVID-19 patients may help in further reducing the transmission of the virus in the community.
Whiplash injury is a frequent traumatic lesion occurring mainly in road accidents, which may also cause dizziness severe enough to impact everyday life. Vestibular examination is routinely performed on these patients, although the role of the neuro-otologist is still not clearly defined. The main endpoint of this study was to describe the videonystagmography (VNG) evidence in a large cohort of patients who underwent road traffic whiplash injury.
717 consecutive patients who reported whiplash-associated disorders due to a road traffic accident underwent clinical examination and VNG.
Patients with saccadic test latency anomalies more frequently complained of vertigo, nausea and cochlear symptoms after trauma (p=0.031, 0.028 and 0.006), while patients with bilateral vestibular weakness at caloric stimulation more often displayed neck pain after trauma (p=0.005). Patients complaining of positional or cochlear symptoms or with accuracy anomalies at the saccadic test were significantly older than those with no positional, no cochlear symptoms and without accuracy anomalies (p=0.022, p=0.034 and p=0.001). Patients with bilateral vestibular hypofunction were significantly younger (p<0.001).
VNG evidence, particularly vestibular function and saccadic tests, may be related to damage in the cervical region due to whiplash trauma. These findings suggest that neuro-otologic examination may play a role in properly identifying those who suffer damage caused by whiplash trauma, and in characterizing the severity and prognosis of whiplash-associated disorders.
VNG evidence, particularly vestibular function and saccadic tests, may be related to damage in the cervical region due to whiplash trauma. These findings suggest that neuro-otologic examination may play a role in properly identifying those who suffer damage caused by whiplash trauma, and in characterizing the severity and prognosis of whiplash-associated disorders.
To investigate the effect of combination therapy (fluoxetine + alprazolam) and fluoxetine alone in treatment of tinnitus.
147 participants with chronic tinnitus were divided into three groups (fluoxetine, fluoxetine+ alprazolam, and placebo). Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Tinnitus Severity Index (TSI), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) used to assess tinnitus. Effect size according to partial Eta square calculated and level of significance was considered as P<0.05.
Fluoxetine reduced VAS, THI, BDI, and increased BAI. The combination therapy significantly reduced VAS, THI, BAI, and BDI. None of them reduced the TSI. The effect size for BAI and BDI were 0.135 (medium) and 0.075 (small), respectively. There was no significant difference between combination and single-drug therapy.
Both groups improved THI and VAS. Combination therapy was not significantly different from single-drug treatment. Combination therapy can be considered only according to the psychiatric needs of patients.
Both groups improved THI and VAS. Combination therapy was not significantly different from single-drug treatment. Combination therapy can be considered only according to the psychiatric needs of patients.
The value of parotidectomy in older patients is unclear. This study presents a decision model to help resolve this question.
A Markov model with Monte Carlo simulation was used to compare outcomes in patients of different ages with pleomorphic adenoma of the parotid gland treated by surgery or surveillance.
In 30-year-old patients, surgery conferred a 3.5-year gain in life expectancy whereas in 75-year-olds, it was only 0.74months. The expected rate of malignant transformation at age 30years was 6.5% after surgery and 26.5% after surveillance; at age 65, corresponding rates were 0.8% and 10.7%. Sensitivity analysis showed that age was the only parameter that significantly contributed to life expectancy. The benefit of surgery was restricted in older patients.
Our Markov decision-analysis model suggests that patients older than 65years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.
Our Markov decision-analysis model suggests that patients older than 65 years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.
Coronavirus disease 2019 (COVID-19) is an infectious disease that leads to critical respiratory problems. Obstructive sleep apnea (OSA) is the most common sleep-associated breathing disease and is represented by repetitive experiences of constraint of the respiratory tract prompting to reduced or deficient breathing during sleep. Auto-Continuous positive airway pressure (Auto-CPAP) is a modality of respiratory ventilation used as gold standart in the treatment of OSA.
This study was performed to conclude the alteration of Auto-CPAP levels in OSA patients who had COVID-19 history.
Nineteen OSA patients who had cured COVID-19 and used Auto-CPAP were included in this study. Nightly Auto-CPAP 95th percentile pressure (95thpp), median CPAP pressure and AHI before COVID-19 disease and one month after COVID therapy were recorded from electronic cards of Auto-CPAP devices.
Before COVID infection, average Auto-CPAP 95thpp was 8.56±0.17 cm H
O. One month after COVID-19, average Auto-CPAP 95thpp was 9.78±0.21 cm H
O (P<0.01). While Median CPAP pressure was 7.49±0.16 cm H
O before COVID, it was found to be 8.15±0.19 cm H
O after the disease (P<0.01).
The increase in need of average Auto-CPAP 95thpp and median CPAP pressure in OSA patients who have had COVID-19 disease and use Auto-CPAP shows that this disease causes problems in both the lower and upper airways.
The increase in need of average Auto-CPAP 95thpp and median CPAP pressure in OSA patients who have had COVID-19 disease and use Auto-CPAP shows that this disease causes problems in both the lower and upper airways.
Provide data to support expansion of FDA indications for the Bone anchored hearing system (BAHS).
This retrospective study in a tertiary otologic referral center included106 consecutive subjects who were implanted with a Bone Anchored Hearing System (BAHS) between January 2009 and January 2015 for single sided deafness. Subjects were divided into three groups by bone conduction pure tone average (PTA) of the better hearing ear 0-20dB (group 1), 21-40dB (group 2) and 41-55dB (group 3). All patients underwent BAHS implantation. Speech perception data (Hearing In Noise Test and Consonant-Nucleus-Consonant testing) was collected before and after surgical intervention. Patient-reported quality of life measures were obtained at least 6months after activation. These included the Abbreviated Profile of Hearing Aid Benefit and Glasgow Benefit Inventory.
All three groups of subjects demonstrated statistically significant improvement in outcome measures following BAHS. Subject reported quality of life outcome measures demonstrated significant improvement in disability from hearing loss and in quality of life.
Patients with single sided deafness who have bone conduction thresholds worse than 20dB in their contralateral ear are still able to benefit significantly from BAHS.
Patients with single sided deafness who have bone conduction thresholds worse than 20 dB in their contralateral ear are still able to benefit significantly from BAHS.
To report a unique case of salivary duct cyst presenting as parapharyngeal space mass and review relevant literature regarding salivary duct cyst and fine needle aspiration biopsy of salivary gland lesions.
After a case description, a review of the literature regarding salivary duct cyst etiology, pathophysiology, presentation, histologic features, and the accuracy of FNA in the context of salivary gland lesions was conducted.
Salivary duct cysts are rare, often acquired, cystic dilatations of salivary ducts thought to arise secondary to ductal obstruction, commonly occurring in the major salivary glands. Fine needle aspiration is the biopsy method of choice for most head and neck lesions. There is controversy surrounding this method in salivary lesions, but recent data indicates it can be just as reliable as in other locations.
Here, we highlight a patient with a salivary duct cyst presenting as a parapharyngeal mass, which has not been described in the literature. Overall, FNA in salivary lesions is highly pathologist dependent, which likely contributes to varying accuracy in the literature.
Homepage: https://www.selleckchem.com/products/GSK690693.html
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